A RESOURCE FOR DEVELOPMENTAL REGULATORY GENOMICS PROJECT SUMMARY This proposal seeks support for a sea urchin Resource for Developmental Regulatory Genomics. In the past 5- 10 years, the sea urchin has become a pre-eminent model for analysis of the genomic control of spatial gene expression during embryonic development. The most complete gene regulatory networks (GRNs) for development that we have for any animal have recently been solved for sea urchin embryos. GRNs constitute the transformation function between the genomic sequence and the expression of transcription factor-encoding genes, which play a cardinal role in driving developmental processes. Therefore, current GRN research on sea urchin embryos has great general significance for our understanding of all genomically encoded processes of animal development. The proposal is founded on a recent, comprehensive, community-wide assessment of activities that are now of the highest priority in order to enhance the utility of this research model for regulatory genomics. The aims include: a) expanded use of recombineered, bacterial artificial chromosome (BAC) reporters for cis-regulatory analysis (a unique focus of this model system) and for many other applications; b) the creation of new community-wide resources to dramatically speed and enhance the analysis of GRNs; and c) the refinement of gene perturbation technologies to probe changes in GRN architecture over time and to provide access to previously intractable gene regulatory interactions in specific cell types. Every one of these aims capitalizes on (and extends) the experimental advantages of sea urchins for regulatory systems biology. In the aggregate, they will create a tool kit currently not available for ANY developing animal system and will have a dramatic impact on the community of researchers engaged in the regulatory biology of development. The biomedical implications relevant to the NIH mission are twofold. First, failures of human development are common and to identify their causes it will be essential to understand the complex genetic programs that drive embryonic development. Second, it is now widely recognized that most human genetic diseases are a result of the mis-regulation of gene expression. The resources created by this project will spur basic research that will help us to better understand the control of gene expression in animal cells.